Acta crystallographica. Section F, Structural biology communications最新文献_第2页

Crystal structure of the folded domains of Xrs2 from Saccharomyces cerevisiae. 酿酒酵母Xrs2折叠结构域的晶体结构。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-09-01 Epub Date: 2025-08-06 DOI: 10.1107/S2053230X25006867

Ajeak Vigneswaran, Ke Shi, Hideki Aihara, Robert L Evans, Michael P Latham

引用次数: 0

Crystal structure of a seven-substitution mutant of hydroxynitrile lyase from rubber tree. 橡胶树羟基腈裂解酶七取代突变体的晶体结构。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-09-01 Epub Date: 2025-08-27 DOI: 10.1107/S2053230X25007034

Colin T Pierce, Lauren R Greenberg, Meghan E Walsh, Ke Shi, Drenen J Magee, Hideki Aihara, Wendy Gordon, Robert L Evans, Romas J Kazlauskas

{"title":"Crystal structure of a seven-substitution mutant of hydroxynitrile lyase from rubber tree.","authors":"Colin T Pierce, Lauren R Greenberg, Meghan E Walsh, Ke Shi, Drenen J Magee, Hideki Aihara, Wendy Gordon, Robert L Evans, Romas J Kazlauskas","doi":"10.1107/S2053230X25007034","DOIUrl":"10.1107/S2053230X25007034","url":null,"abstract":"The α/β-hydrolase fold superfamily includes esterases and hydroxynitrile lyases which, despite catalyzing different reactions, share a Ser-His-Asp catalytic triad. We report a 1.99 Å resolution crystal structure of HNL6V, an engineered variant of hydroxynitrile lyase from Hevea brasiliensis (HbHNL) containing seven amino-acid substitutions (T11G, E79H, C81L, H103V, N104A, G176S and K236M). The structure reveals that HNL6V maintains the characteristic α/β-hydrolase fold while exhibiting systematic shifts in backbone and catalytic atom positions. Compared with wild-type HbHNL, the Cα positions in HNL6V differ by a mean of 0.2 ± 0.1 Å, representing a statistically significant displacement. Importantly, the catalytic triad and oxyanion-hole atoms have moved 0.2-0.8 Å closer to their corresponding positions in SABP2, although they remain 0.3-1.1 Å from fully achieving the configuration of SABP2. The substitutions also increase local flexibility, particularly in the lid domain covering the active site. This structural characterization demonstrates that targeted amino-acid substitutions can systematically shift catalytic geometries towards those of evolutionarily related enzymes.","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":"81 Pt 9","pages":"398-405"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Triosephosphate isomerase from Fasciola hepatica: high-resolution crystal structure as a drug target. 肝片形吸虫三磷酸异构体酶：高分辨率晶体结构作为药物靶点。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-09-01 Epub Date: 2025-08-20 DOI: 10.1107/S2053230X25006454

Georgios Kontellas, David J Studholme, Mark van der Giezen, David J Timson, Jennifer A Littlechild, Michail N Isupov

引用次数: 0

Off-target binding of the histone deacetylase inhibitor vorinostat to carbonic anhydrase II and IX. 组蛋白去乙酰化酶抑制剂伏立诺他与碳酸酐酶II和IX的脱靶结合。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-09-01 Epub Date: 2025-08-26 DOI: 10.1107/S2053230X25007447

Mitchell C Gulkis, James T Hodgkinson, Céleste P Sele, Wolfgang Knecht, Robert McKenna, S Zoë Fisher

{"title":"Off-target binding of the histone deacetylase inhibitor vorinostat to carbonic anhydrase II and IX.","authors":"Mitchell C Gulkis, James T Hodgkinson, Céleste P Sele, Wolfgang Knecht, Robert McKenna, S Zoë Fisher","doi":"10.1107/S2053230X25007447","DOIUrl":"10.1107/S2053230X25007447","url":null,"abstract":"Histone deacetylase inhibitors (HDACi) are widely used in cancer therapy but often suffer from off-target effects due to their pan-inhibitory activity towards zinc-dependent enzymes. Vorinostat (SAHA), a hydroxamate-based HDACi, has been shown to lack isoform selectivity, potentially leading to unintended interactions with other metalloenzymes. Here, we report high-resolution crystal structures of SAHA bound to human carbonic anhydrase II (CA II) and a carbonic anhydrase IX (CA IX) active-site mimic. Structures determined at room temperature and 100 K revealed two distinct SAHA conformers in both CA II and the CA IX mimic, with the hydroxamate moiety displacing the zinc-bound water and adopting either a tetrahedral or pentahedral coordination to Zn2+. Differences in hydrophobic interactions were observed between CA II and the CA IX mimic due to the F131V amino-acid difference between the two enzymes. SwissDock modeling accurately predicted the SAHA binding orientations observed in crystallography. Thermal shift assays using nanoDSF showed minimal stabilization of either CA by SAHA, in contrast to the potent CA inhibitor acetazolamide. Binding-energy calculations suggest that SAHA may bind carbonic anhydrases with affinities comparable to its HDAC targets. These findings highlight potential off-target binding of SAHA to carbonic anhydrases, which may contribute to its clinical side effects. The results also suggest that hydroxamates may serve as a nonsulfonamide scaffold for novel CA inhibitors, although isoform selectivity remains a challenge.","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":"81 Pt 9","pages":"388-397"},"PeriodicalIF":1.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12400194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144938480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Crystal structure of the virulence protein J (VirJ) domain 1 from Brucella abortus 流产布鲁氏菌毒力蛋白J （VirJ）结构域1的晶体结构

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-08-18 DOI: 10.1107/S2053230X25006697

Chloé Dugelay, Sibylle Ferrarin, Laurent Terradot

引用次数: 0

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-08-06

引用次数: 0

Crystal structures of Escherichia coli glucokinase and insights into phosphate binding. 大肠杆菌葡萄糖激酶的晶体结构和对磷酸盐结合的见解。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-08-01 Epub Date: 2025-07-09 DOI: 10.1107/S2053230X25005515

Joseph Andrews, Joshua Sakon, Chenguang Fan

{"title":"Crystal structures of Escherichia coli glucokinase and insights into phosphate binding.","authors":"Joseph Andrews, Joshua Sakon, Chenguang Fan","doi":"10.1107/S2053230X25005515","DOIUrl":"10.1107/S2053230X25005515","url":null,"abstract":"Here, we report the crystal structure of Escherichia coli glucokinase (GLK), which has phosphate bound in the cleft between the α and β domains adjacent to the active site. A ternary complex consisting of GLK, glucose and phosphate is also reported in this work. Diffraction data were collected at 2.63 Å resolution for the phospate-bound form (Rwork/Rfree = 0.191/0.230) and at 2.54 Å resolution for the ternary complex (Rwork/Rfree = 0.202/0.258), both at 297 K. A B-factor analysis of the phosphate-bound GLK structure revealed consistently lower values for phosphate-interacting basic residues in the α4, α5 and α9 helices, while significant root-mean-square deviation (r.m.s.d.) spikes indicated flexibility in regions preceding β1 and within the loop between the β5 and β6 sheets of the α domain. In the ternary complex, phosphate is bound adjacent to glucose, and the B factors for the α4, α5 and α9 helices were further reduced, while r.m.s.d. spikes were observed at the end of the β10 sheet and within the α6 helix of the β-domain. This structural characterization suggests that phosphate could influence the activity of GLK by altering glucose binding and modulating interactions with a loop-interacting regulatory protein.","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":" ","pages":"332-337"},"PeriodicalIF":1.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144590222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nucleotide-bound crystal structures of the SARS-CoV-2 helicase NSP13. SARS-CoV-2解旋酶NSP13的核苷酸结合晶体结构

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-08-01 Epub Date: 2025-07-10 DOI: 10.1107/S2053230X25005266

Patrick Kloskowski, Piotr Neumann, Annette Berndt, Ralf Ficner

引用次数: 0

Structures of Listeria monocytogenes MenD in ThDP-bound and in-crystallo captured intermediate I-bound forms. 单核增生李斯特菌的thdp结合和晶体捕获的中间i结合形式的MenD结构。

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-08-01 Epub Date: 2025-07-17 DOI: 10.1107/S2053230X25006181

Michelle Bailey, Fiona M Given, Ngoc Anh Thu Ho, F Grant Pearce, Timothy M Allison, Jodie M Johnston

{"title":"Structures of Listeria monocytogenes MenD in ThDP-bound and in-crystallo captured intermediate I-bound forms.","authors":"Michelle Bailey, Fiona M Given, Ngoc Anh Thu Ho, F Grant Pearce, Timothy M Allison, Jodie M Johnston","doi":"10.1107/S2053230X25006181","DOIUrl":"10.1107/S2053230X25006181","url":null,"abstract":"Menaquinones (vitamin K2) are a family of redox-active small lipophilic molecules that serve as vital electron carriers in many bacterial electron-transport pathways. The ThDP-dependent enzyme 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate (SEPHCHC) synthase (MenD) catalyses the first irreversible step in bacterial classical menaquinone biosynthesis via a series of reactions involving covalent ThDP-bound intermediates. We report structures of MenD from the pathogen Listeria monocytogenes (LmoMenD) in its ThDP cofactor-bound and in-crystallo captured intermediate I-bound forms. Analysis of the structures revealed that LmoMenD adopts the typical three-domain ThDP-dependent fold observed for MenD orthologs, while a combination of structure, size-exclusion chromatography, mass photometry and small-angle X-ray scattering analysis showed that the enzyme has a homotetrameric quaternary structure. While both of the ligand-bound structures reported here were very similar, comparison with an apo form from the PDB revealed a closing down of the active site in the ligand-bound forms, with more complete models suggesting lower levels of disorder around key regions of the active site that interface with ThDP or the captured intermediate. Enzyme kinetics characterization showed the enzyme was active and enabled allosteric inhibition to be measured. There was weak inhibition of enzyme activity in the presence of 1,4-dihydroxy-2-naphthoic acid, an allosteric regulator of Mycobacterium tuberculosis MenD and downstream metabolite in the menaquinone-biosynthesis pathway.","PeriodicalId":7029,"journal":{"name":"Acta crystallographica. Section F, Structural biology communications","volume":" ","pages":"348-357"},"PeriodicalIF":1.1,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12312563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 1.1 4区生物学

Acta crystallographica. Section F, Structural biology communications Pub Date : 2025-07-31

引用次数: 0